Perinatally HIV-Infected Youths After Transition from Pediatric to Adult Care,a Single-Center Experience from Northern Italy

Editor: as a consequence of the development of combination antiretroviral therapy (cART) at the end of the nineties, the first generation of perinatally HIV-infected children has reached young adulthood. ¹

A retrospective, single-center study was conducted on perinatally HIV-infected young patients after transition from pediatric to adult care in Brescia, Northern Italy. Patients were followed with 3 monthly scheduled blood examinations (complete blood count and biochemical routine, CD4⁺ T cells count, and HIV-RNA) and clinical evaluations. HIV-RNA was defined undetectable if <50 copies/mL.

Twenty-four patients were transferred to Infectious Disease Outpatient Clinic from 2004 to 2016 at a median age of 18 years (interquartile range [IQR] 17.5–19, range 9–24 years). 37.5% were male, and 75% were Italian. Median CD4⁺ T-cell count at transition was 534 cell/μL; 9/24 presented detectable HIV-RNA. At transition, cART regimen was protease inhibitors (PI)-based in 17/24 (70.8%) patients, non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based in 5 (20.8%) cases, and integrase inhibitors (InSTI)-based in only 2 youths (Table 1). Median duration of cART at transition was 14 years (IQR 6–17 years, data available for 17/24 patients).

Two patients faced AIDS-defining events after transition: one patient experienced recurrent pneumonia (CD4⁺ T cells <200 cell/μL, HIV-RNA 9,500 copies/mL due to nonadherence at the clinical event, 26 months after transition), and a patient was lost to follow-up for 2 years and then diagnosed with progressive multifocal leukoencephalopathy (CD4⁺ 57 cell/μL, HIV-RNA 4,769 copies/mL, 57 months after transition). At the end of follow-up (median 52 months), 80% of patients were in care, while 5 young patients were lost to follow-up (at a median time of 55 months after transition, IQR 35–97, range 26–104 months) and should be considered as failures. Three out of five patients lost to follow-up presented detectable HIV-RNA both at transition and at the last point of follow-up.

One hundred percent of patients on follow-up were treated with cART (11/19 InSTI-based regimen, Table 1). cART regimen was modified in 14/19 patients (in 13/19 youths cART regimen was modified at least twice; median of two changes after transition), more frequently with single substitutions of drugs (in 81.1% of cases), for virological failure, intolerance, or optimization. In 67.2% of cases, core agent was modified (63.2% of cases at first change after transition).

Median adherence to scheduled follow-up, based on number of missed visits, was 97.3% (IQR 88.8%–100%, range 66.6%–100%).

Median CD4⁺ T-cell count was 626 cell/μL 12 months after transition and 716 cell/μL at the end of follow-up; HIV-RNA was <50 copies/mL in 75% of patients at month 12 after transition and in all patients still in care at the end of follow-up (Table 1). Resistance testing was available for 13/19 patients showing resistance-associated mutations (RAMs) in 69.2% of patients (Table 1). Out of those with mutations detected, 100% harbored a virus with reduced susceptibility to nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; RAMs most frequently detected were M41L, D67N, M184V, L210W, T215Y), 3/9 patients showed resistance to both NRTIs and NNRTIs and 3/9 patients to both NRTIs and PIs.

In the last few years, the first case series of perinatally HIV-infected children reaching young adulthood were published. ² Studies have reported lower rates of viral suppression, due to adherence issues, resulting in the emergence of resistance. Transition to adult care has also been identified as a critical point. ³ Some authors, showing viral suppression maintenance on suboptimal cART regimens, questioned about the opportunity of optimizing cART regimens, with the risk of reduced adherence and potential side effects onset. ² Even with the limitation of small cohort size, we point out a satisfactory outcome of perinatally HIV-infected young adults after transition to adult care, with no deaths and only two AIDS-defining events in patients on follow-up, through cART optimization with InSTI. cART regimen was modified in the vast majority of patients after transition, in the effort to individualize cART, to avoid side effects and intolerance. In conclusion, with the availability of more potent and better-tolerated drugs, optimization of cART is possible also in this previously difficult-to-treat group of patients. To note, five young patients were lost to follow-up in our cohort highlighting the need for better strategies to retain into care this peculiar group of patients.